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环境富集增强了具有阿尔茨海默氏症样病理的转基因小鼠的细胞可塑性。

Environmental enrichment enhances cellular plasticity in transgenic mice with Alzheimer-like pathology.

作者信息

Herring Arne, Ambrée Oliver, Tomm Manuel, Habermann Henrik, Sachser Norbert, Paulus Werner, Keyvani Kathy

机构信息

Institute of Neuropathology, University Hospital Muenster, Muenster, Germany.

出版信息

Exp Neurol. 2009 Mar;216(1):184-92. doi: 10.1016/j.expneurol.2008.11.027. Epub 2008 Dec 11.

Abstract

Alzheimer's disease (AD) is accompanied by hippocampal neuronal loss and abnormal neurogenesis, both of which probably contributing to AD-related cognitive deficits. Mounting evidence indicates that cognitive and physical stimulation provided by environmental enrichment improves neurogenesis in healthy animals and counteracts beta-amyloid pathology in mouse models of AD. Here, we hypothesized that environmental enrichment has also an impact on hippocampal neurogenesis in mice with AD-like pathology. Therefore, TgCRND8 mice and wild type littermates were either housed under standard conditions or in an enriched environment for 4 months. Standard housed TgCRND8 mice revealed diminished hippocampal cell proliferation and reduced number of mature newborn neurons compared to wild type littermates under the same housing condition. However, environmental enrichment reversed this genotype effect. Here, we show that cognitive and physical stimulation is capable of increasing the number of newborn mature hippocampal neurons in transgenic mice to wild type levels. Moreover, the expression of various plasticity associated molecules was enhanced in transgenic mice due to enriched housing. This study identifies that environmental enrichment improves diminished cellular plasticity in AD brain, probably enhancing the brain capacity to better compensate for neurodegeneration.

摘要

阿尔茨海默病(AD)伴有海马神经元丢失和异常神经发生,这两者都可能导致与AD相关的认知缺陷。越来越多的证据表明,环境丰富化所提供的认知和身体刺激可改善健康动物的神经发生,并抵消AD小鼠模型中的β-淀粉样蛋白病理。在此,我们假设环境丰富化对具有AD样病理的小鼠的海马神经发生也有影响。因此,将TgCRND8小鼠和野生型同窝小鼠分别饲养在标准条件下或丰富环境中4个月。与在相同饲养条件下的野生型同窝小鼠相比,标准饲养的TgCRND8小鼠海马细胞增殖减少,成熟新生神经元数量减少。然而,环境丰富化逆转了这种基因型效应。在此,我们表明认知和身体刺激能够将转基因小鼠新生成熟海马神经元的数量增加到野生型水平。此外,由于饲养环境丰富,转基因小鼠中各种可塑性相关分子的表达增强。本研究表明,环境丰富化可改善AD大脑中降低的细胞可塑性,可能增强大脑更好地补偿神经退行性变的能力。

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